M. Kwiatkowski (Maciej)http://repub.eur.nl/ppl/26568/
List of Publicationsenhttp://repub.eur.nl/eur_signature.pnghttp://repub.eur.nl/
RePub, Erasmus University RepositoryScreening and prostate cancer mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-uphttp://repub.eur.nl/pub/59567/
Mon, 11 Aug 2014 00:00:01 GMT<div>F.H. Schröder</div><div>J. Hugosson</div><div>M.J. Roobol-Bouts</div><div>T.L. Tammela</div><div>M. Zappa</div><div>V. Nelen</div><div>M. Kwiatkowski</div><div>M. Lujan</div><div>L. Määttänen</div><div>H. Lilja</div><div>L.J. Denis</div><div>F. Recker</div><div>A. Páez</div><div>C.H. Bangma</div><div>S. Carlsson</div><div>D. Puliti</div><div>A. Villers</div><div>X. Rébillard</div><div>M. Hakama</div><div>U-H. Stenman</div><div>P.M. Kujala</div><div>K. Taari</div><div>G. Aus</div><div>A. Huber</div><div>Th.H. van der Kwast</div><div>R.H.N. van Schaik</div><div>H.J. de Koning</div><div>S.M. Moss</div><div>A. Auvinen</div>
Background: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. Methods: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. Findings: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88). Interpretation: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Funding: Each centre had its own funding responsibility.A different method of evaluation of the ERSPC trial confirms that prostate-specific antigen testing has a significant impact on prostate cancer mortalityhttp://repub.eur.nl/pub/61052/
Wed, 01 Jan 2014 00:00:01 GMT<div>M. Zappa</div><div>D. Puliti</div><div>J. Hugosson</div><div>F.H. Schröder</div><div>P. van Leeuwen</div><div>R. Kranse</div><div>A. Auvinen</div><div>S. Carlsson</div><div>M. Kwiatkowski</div><div>V. Nelen</div><div>A.P. Borda</div><div>M.J. Roobol-Bouts</div><div>A. Villers</div>
The advantages and disadvantages of two different methods of analyzing the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with respect to the effect of prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality (ie, disease-specific mortality analysis and excess mortality analysis) are discussed in depth. The traditional disease-specific mortality is the best end point, but it could be biased by misclassification of causes of death, and it does not take into account the possible effect of the screening process on other causes of death. Excess mortality analysis overcomes these problems, but the results could be biased if the expected mortality is not corrected for attendance status. Both methods, when applied to the ERSPC trials, demonstrate that no increase in non-PCa mortality occurred in the screening group and confirm that PSA screening decreases PCa mortality.Prostate cancer: ESMO consensus conference guidelines 2012http://repub.eur.nl/pub/66274/
Wed, 01 May 2013 00:00:01 GMT<div>A. Horwich</div><div>J. Hugosson</div><div>T.M. de Reijke</div><div>T. Wiegel</div><div>K. Fizazi</div><div>V. Kataja</div><div>C. Parker</div><div>J. Bellmunt</div><div>D.R. Berthold</div><div>A. Bill-Axelson</div><div>S. Carlsson</div><div>G. Daugaard</div><div>G. de meerleer</div><div>T. de reijke</div><div>D. Dearnaley</div><div>K. Fizazi</div><div>V. Fonteyne</div><div>S. Gillessen</div><div>D. Heinrich</div><div>J. Hugosson</div><div>V. Kataja</div><div>M. Kwiatkowski</div><div>S. Nilsson</div><div>A. Padhani</div><div>C. Papandreou</div><div>M.J. Roobol-Bouts</div><div>A. Sella</div><div>R. Valdagni</div><div>Th.H. van der Kwast</div><div>P.C.M.S. Verhagen</div><div>T. Wiegel</div>
The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.Screening for prostate cancer decreases the risk of developing metastatic disease: Findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC)http://repub.eur.nl/pub/37453/
Thu, 01 Nov 2012 00:00:01 GMT<div>F.H. Schröder</div><div>J. Hugosson</div><div>S. Carlsson</div><div>T.L. Tammela</div><div>L. Määttänen</div><div>A. Auvinen</div><div>M. Kwiatkowski</div><div>F. Recker</div><div>M.J. Roobol-Bouts</div>
Background: Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal. Objective: To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial. Design, setting, and participants: Data were available for 76 813 men aged 55-69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up. Intervention: Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm. Outcome measurements and statistical analysis: The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease. Results and limitations: After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60-0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41-0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up. Conclusions: PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736. Quality-of-life effects of prostate-specific antigen screeninghttp://repub.eur.nl/pub/39092/
Thu, 16 Aug 2012 00:00:01 GMT<div>E.A.M. Heijnsdijk</div><div>E.M. Wever</div><div>A. Auvinen</div><div>J. Hugosson</div><div>S. Ciatto</div><div>V. Nelen</div><div>M. Kwiatkowski</div><div>A. Villers</div><div>A. Páez</div><div>S.M. Moss</div><div>M. Zappa</div><div>T.L. Tammela</div><div>T. Mäkinen</div><div>S. Carlsson</div><div>I.J. Korfage</div><div>M.L.E. Essink-Bot</div><div>S.J. Otto</div><div>G. Draisma</div><div>C.H. Bangma</div><div>M.J. Roobol-Bouts</div><div>F.H. Schröder</div><div>H.J. de Koning</div>
Background: After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain. Methods: On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled. Results: Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56). Conclusions: The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.) Copyright Prostate-cancer mortality at 11 years of follow-uphttp://repub.eur.nl/pub/64379/
Thu, 15 Mar 2012 00:00:01 GMT<div>F.H. Schröder</div><div>J. Hugosson</div><div>M.J. Roobol-Bouts</div><div>T.L. Tammela</div><div>S. Ciatto</div><div>V. Nelen</div><div>M. Kwiatkowski</div><div>M. Lujan</div><div>H. Lilja</div><div>M. Zappa</div><div>L.J. Denis</div><div>F. Recker</div><div>A. Páez</div><div>L. Määttänen</div><div>C.H. Bangma</div><div>G. Aus</div><div>S. Carlsson</div><div>A. Villers</div><div>X. Rébillard</div><div>Th.H. van der Kwast</div><div>P.M. Kujala</div><div>B.G. Blijenberg</div><div>U-H. Stenman</div><div>A. Huber</div><div>K. Taari</div><div>M. Hakama</div><div>S.M. Moss</div><div>H.J. de Koning</div><div>A. Auvinen</div>
BACKGROUND:Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up. METHODS:The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer. RESULTS:After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P = 0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P = 0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality. CONCLUSIONS:Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. CopyrightChange of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancerhttp://repub.eur.nl/pub/21387/
Mon, 01 Nov 2010 00:00:01 GMT<div>S.J. Boevee</div><div>L.D.F. Venderbos</div><div>T.L. Tammela</div><div>V. Nelen</div><div>S. Ciatto</div><div>M. Kwiatkowski</div><div>A. Páez</div><div>B. Malavaud</div><div>J. Hugosson</div><div>M.J. Roobol-Bouts</div>
Objective: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm. Methods: Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N = 82,816) and the control arm (N = 99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006. Results: Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%). Conclusion: Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectant management in both arms of the ERSPC. These observations reflect an increasing rate of opportunistic testing over time in men randomised to the control arm.PSA levels and cancer detection rate by centre in the European Randomized Study of Screening for Prostate Cancerhttp://repub.eur.nl/pub/21391/
Mon, 01 Nov 2010 00:00:01 GMT<div>S.J. Otto</div><div>S.M. Moss</div><div>L. Määttänen</div><div>M.J. Roobol-Bouts</div><div>M. Zappa</div><div>V. Nelen</div><div>M. Kwiatkowski</div><div>A. Villers</div><div>J. Hugosson</div><div>A. Sanchez</div><div>H.J. de Koning</div>
Background: To describe the variation in PSA level by age group and screening round in the ERSPC centres and the variation in cancer detection rates in relation to the underlying prostate cancer incidence. Methods: Individual data on men invited for the first and second screening rounds according to protocol (excluding early recalls and interval cancers) were obtained from the central database of the ERSPC (cut-off date 31st December 2006). Data were compared between and within centres for the core age group (55-69 at entry). The cancer detection rate (CDR) was compared with the expected background prostate cancer incidence rate in the absence of screening adjusted for the incidence rate in non-attenders and the control arm (IRS). Results: Mean PSA values in the age groups 55-59 years and 65-69 years showed little variation by centre, except for the Dutch centre, where an increase from 1.6 to 1.8 ng/ml and a decline from 2.9 to 2.5 ng/ml was observed, respectively. Most tumours were detected at the PSA range 4.0-9.9 ng/ml, with a shift to more cancer detection at 3.0-3.9 ng/ml in the second screening round. There was high variability in the CDR between the centres in both the first (16-46 per 1000) and the second screening rounds (14-50 per 1000). Although the ratio CDR/IRS was less variable, it is somewhat lower in Italy and Switzerland (12 and 14,respectively) and higher in the Netherlands (28), than in most other centres and in Belgium the ratio increased markedly, from 20 to 44 between the first and second rounds. Conclusion: There was no clear evidence of a relationship between the underlying incidence and mean PSA levels at screening or the cancer detection rate.The effect of study arm on prostate cancer treatment in the large screening trial ERSPChttp://repub.eur.nl/pub/27565/
Sat, 15 May 2010 00:00:01 GMT<div>T. Wolters</div><div>M.J. Roobol-Bouts</div><div>E.W. Steyerberg</div><div>R.C.N. van den Bergh</div><div>C.H. Bangma</div><div>J. Hugosson</div><div>S. Ciatto</div><div>M. Kwiatkowski</div><div>A. Villers</div><div>M. Lujan</div><div>V. Nelen</div><div>T.L. Tammela</div><div>F.H. Schröder</div>
Prostate cancer (PC) mortality is the most valid end-point in screening trials, but could be influenced by the choice of initial treatment if treatment has an effect on mortality. In this study, PC treatment was compared between the screening and control arms in a screening trial. Data were collected from the European Randomized Study of Screening for Prostate Cancer (ERSPC). The characteristics and initial treatment of PC cases detected in the screening and the control arm were compared. Polytomous logistic regression analysis was used to assess the influence of study arm on treatment, adjusting for potential confounders and with statistical imputation of missing values. A total of 8,389 PC cases were detected, 5,422 in the screening arm and 3,145 in the control arm. Polytomous regression showed that trial arm was associated with treatment choice after correction for missing values, especially in men with high-risk PC. A control subject with high-risk PC was more likely than a screen subject to receive radiotherapy (OR: 1.43, 95% CI: 1.01-2.05, p = 0.047), expectant management (OR: 2.92, 95% CI: 1.33-6.42, p = 0.007) or hormonal treatment (OR: 1.77, 95% CI: 1.07-2.94, p = 0.026) instead of radical prostatectomy. However, trial arm had only a minor role in treatment choice compared to other variables. In conclusion, a small effect of trial arm on treatment choice was seen, particularly in men with high-risk PC. Therefore, differences in treatment between arms are unlikely to play a major role in the interpretation of the results of the ERSPC. Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)http://repub.eur.nl/pub/24365/
Thu, 01 Oct 2009 00:00:01 GMT<div>M.J. Roobol-Bouts</div><div>M. Kerkhof</div><div>F.H. Schröder</div><div>J. Cuzick</div><div>P. Sasieni</div><div>M. Hakama</div><div>U.H. Stenman</div><div>S. Ciatto</div><div>V. Nelen</div><div>M. Kwiatkowski</div><div>M. Lujan</div><div>H. Lilja</div><div>M. Zappa</div><div>L.J. Denis</div><div>F. Recker</div><div>A. Berenguer</div><div>M. Ruutu</div><div>P.M. Kujala</div><div>C.H. Bangma</div><div>G. Aus</div><div>T.L. Tammela</div><div>A. Villers</div><div>X. Rébillard</div><div>S.M. Moss</div><div>H.J. de Koning</div><div>J. Hugosson</div><div>A. Auvinen</div>
Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening. Screening and prostate-cancer mortality in a randomized european studyhttp://repub.eur.nl/pub/32574/
Thu, 26 Mar 2009 00:00:01 GMT<div>F.H. Schröder</div><div>J. Hugosson</div><div>M.J. Roobol-Bouts</div><div>T.L. Tammela</div><div>S. Ciatto</div><div>V. Nelen</div><div>M. Kwiatkowski</div><div>M. Lujan</div><div>H. Lilja</div><div>M. Zappa</div><div>L.J. Denis</div><div>F. Recker</div><div>A.B. Määpttänen</div><div>C.H. Bangma</div><div>G. Aus</div><div>A. Villers</div><div>X. Rébillard</div><div>Th.H. van der Kwast</div><div>B.G. Blijenberg</div><div>S.M. Moss</div><div>H.J. de Koning</div><div>A. Auvinen</div>
Background The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen(PSA) testing on death rates from prostate cancer. Methods We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. Results In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80(95% confidence interval [CI], 0.65 to 0.98; adjusted P = 0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round(excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73(95% CI, 0.56 to 0.90). Conclusions PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis.(Current Controlled Trials number, ISRCTN49127736.) Copyright